Chitosan micelles

Qu G, Yao Z et al (2009) PEG conjugated N-octyl-O-sulfate chitosan micelles for dehvery of paclitaxel in vitro characterization and in vivo evaluation. Eur J Pharm Sci 37 98-105... 

Xiangyang X, Ling L et al (2007) Preparation and characterization of N-succinyl-N -octyl chitosan micelles as doxorubicin carriers for effective anti-tumor activity. Colloids Surf B 55 222-228... 

N-octyl-O-sulfate chitosan Micelles Drug carrier/reduce toxicity and improve bioavailability New formulation of Paclitaxel (Taxol)-PTX with better efficacy and fewer side effects for cancer treatment... 

Hu et al. encapsulated chlorine e6 (Ce6) in stearic acid-grafted chitosan micelles [76]. The size of micelles was 270-300 nm and they could contain 5-20% Ce6. They were stable spherical nanostructure in aqueous condition and enabled sustained release of Ce6 over 12 h. Importantly, they could enhance the uptake of Ce6 to A549 (human lung cancer) and HeLa (human cervix carcinoma) cells, and showed high phototoxicity, proving their potential for cancer therapy. 

Within the small intestine, bile-acid binding interferes with micelle formation. Nauss et al. [268] reported that, in vitro, chitosan binds bile acid micelles in toto, with consequent reduced assimilation of all micelle components, i.e., bile acids, cholesterol, monoglycerides and fatty acids. Moreover, in vitro, chitosan inhibits pancreatic lipase activity [269]. Dissolved chitosan may further depress the activity of lipases by acting as an alternative substrate [270]. 

The ability of chitosan to form complexes is of particular interest. Being slightly basic, it will readily form complexes with anionic compounds. Initially it forms into micelles with small amounts of anionic surfactants, leading to precipitation of a complex as the concentration of the anionic surfactant increases. Chitosan will complex with anionic... 

Zhang, C., Ding, Y., Ping, Q.E., Yu, L.L. (2006). Novel chitosan-derived nanomaterials and their micelle-forming properties. Journal of Agricultural and Food Chemistry, 54, 8409-8416. 

Let us consider now the case of a specific ionic polysaccharide. The unique properties of complexes of the cationic chitosan with non-ionic sorbitan esters provides an interesting example. Grant and co-workers (2006) have established that mixtures of chitosan and surfactant form emulsion-like solutions and/or creams, where the surfactant component is present as droplets or micelle-like particles and the chitosan solution acts as the system s continuous phase. It was established that the length and the degree of saturation of the surfactant hydrocarbon chain have a significant impact on the development of the chitosan-surfactant complexes. Moreover, an optimal distance between the chitosan s protonated amine groups is required for effective interactions to occur between the polysaccharide and the sorbitan esters. 

According to Groot (2000), the mechanism of interaction between a polymer and surfactant may be deduced by considering parameters such as polymer size, mode of surfactant adsorption (continuous or discrete micelles), and possible sites of interaction (head group or tail). For the case of the mechanism of the interaction between chitosan and sorbitan esters, the polymer concentration (dilute, semi-dilute, concentrated) of... 

Hydrophobically modified polymers can associate in aqueous media to form micelle-like structures above their critical association concentrations (CACs). The nanosized self-aggregates were prepared using modified natural polysaccharides such as pullulan, curdlan, and glycol chitosan. The modified polysaccharides provide excellent biocompatibility, biodegradability, low immunogenicity, and biological activities. 

Cationic polymers, such as poly(L-lysine) (PEL), polyethylenimine (PEI), chitosan, polyamidoamine (PAMAM) dendrimers, poly(2-dimethylamino) ethyl methacrylate, and polyphosphoesters, condense DNA to form compacted polyplexes. ° The size and the stability of polyplexes depend on the ratio of cations vs. anions, temperature, ionic strength, and the solvent. Stability of polyplexes can be enhanced by conjugating PEG to the polycations or by using PEG-containing block or graft polymers that form micelles. Small cationic peptides are also able to condense DNA, however, six-consecutive-cations is the minimal requirement to achieve this effectively. 

Many of the poorly soluble drugs included in amphiphilic chitosan-based nanocarriers are anticancer drugs, e.g., paclitaxel, doxorubicine, camptothecin, and Mytomycin C. Besides increasing their solubility, the polymeric micelles... 

Huo M, Zhang Y et al (2010) Synthesis and characterization of low-toxic amphiphilic chitosan derivatives and their application as micelle carrier for antitumor drug. Int J Pharm 394 162-173... 

Zhang C, Ding Y et al (2007) Polymeric micelle systems of hydroxycamptothecin based on amphiphilic N-alkyl-N-trimethyl chitosan derivatives. Colloids Surf B 55 192-199... 

Liu J, Li H et al (2010) Novel pH-sensitive chitosan-derived micelles loaded with pachtaxel. Carbohydr Polym 82 432-439... 

Jiang G-B, Quan D et al (2006) Preparation of polymeric micelles based on chitosan bearing a small amount of highly hydrophobic groups. Carbohydr Polym 66 514—520... 

Du Y-Z, Lu P et al (2010) Stearic acid grafted chitosan oligosaccharide micelle as a promising vector for gene delivery system factors affecting the complexation. Int J Pharm 391 260-266... 

Du Y-Z, Wang L et al (2011) Linoleic acid-grafted chitosan oligosaccharide micelles for intracellular drug delivery and reverse drug resistance of tumor cells. Int J Biol Macromol 48(l) 215-222... 

Ye Y-Q, Yang F-L et al (2008) Core-modified chitosan-based polymeric micelles for controlled release of doxorubicin. Int J Pharm 352 294—301... 

Li Q, Du Y-Z et al (2010) Synthesis of Lamivudine stearate and antiviral activity of stearic acid-g-chitosan oligosaccharide polymeric micelles delivery system. Eur J Pharm Sci 41 498-507... 

Hu F-Q, X-1 Wu et al (2008) Cellular uptake and cytotoxicity of shell crosslinked stearic acid-grafted chitosan oligosaccharide micelles encapsulating doxorubicin. Eur J Pharm Biopharm 69 117-125... 

Zhou Y-Y, Du Y-Z et al (2010) Preparation and pharmacodynamics of stearic acid and poly (lactlc-co-glycolic acid) grafted chitosan oligosaccharide micelles for 10-hydroxycamp-tothecln. Int J Pharm 393 144-152... 

The available data indicate that the hypocholesterolemic and hypolipidemic activity of chitosan is probably due to disruption and/or inhibition of micelle formation. At pH 6.0-6.5 chitosan begins to precipitate and as the linear chains of the polysaccharide start to aggregate, they can entrap the whole micelles. The entrapped cholesterol, fatty acids and monoglycerides thus escape absorption. Such "polar entrapment," shown in Figure 2, can occur in the duodenum. Another mode of action could be the "disintegration" of mixed micelles, which can start before the precipitation of chitosan, and in which the free fatty acids and bile acids are selec-... 

Figure 2. Possible mode of interaction of chitosan with mixed micelles.

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